Gruenwald K et al. – Members of the Leprecan family of proteins include enzymes, prolyl 3–hydroxylase 1 (P3h1), P3h2 and P3h3, and non–enzymatic proteins, Crtap and Sc65. Mutations in CRTAP and LEPRE1 (encoding P3H1) have been associated with human disease such as recessive osteogenesis imperfecta, however, the function of Sc65 which is closely related and highly homologous to Crtap is unknown. Bone loss is due to increased bone resorption mediated by a non–cell autonomous effect on osteoclasts. Therefore, Sc65, like its related family member Crtap, is an important modulator of bone homeostasis, acting as a negative regulator of osteoclastogenesis.